US11779686B2 - Coating for medical devices - Google Patents

Coating for medical devices Download PDF

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Publication number
US11779686B2
US11779686B2 US16/612,994 US201816612994A US11779686B2 US 11779686 B2 US11779686 B2 US 11779686B2 US 201816612994 A US201816612994 A US 201816612994A US 11779686 B2 US11779686 B2 US 11779686B2
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medical device
substrate
functional layer
monosaccharide
coating
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US20200215238A1 (en
Inventor
Uwe Schedler
Christian Heise
Thomas Thiele
Hans Henkes
Hermann Monstadt
Ralf Hannes
Tim Lenz-Habijan
Catrin Bannewitz
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Phenox GmbH
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Phenox GmbH
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/04—Use of organic materials, e.g. acetylsalicylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0076—Chemical modification of the substrate
    • A61L33/0088—Chemical modification of the substrate by grafting of a monomer onto the substrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/06—Use of macromolecular materials
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • C08L33/04—Homopolymers or copolymers of esters
    • C08L33/06—Homopolymers or copolymers of esters of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical
    • C08L33/08—Homopolymers or copolymers of acrylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L83/00—Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
    • C08L83/04—Polysiloxanes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23—Carbohydrates
    • A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/02—Treatment of implants to prevent calcification or mineralisation in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/06—Coatings containing a mixture of two or more compounds

Definitions

  • the invention relates to a coating for medical devices, said coating essentially comprising biomimetic and/or bio-repulsive properties. Aside from this, the invention also relates to a method for the coating of medical devices.
  • thrombocytes also called platelets
  • thrombi blood clots
  • thrombocyte adhesion adheres to the surface of the introduced medical device/product marked by the body's endogenous proteins (thrombocyte adhesion), which as a result may lead to the formation of a thrombus (thrombocyte aggregation).
  • thrombus for example, is caused to be set free in the vascular system, it may give rise to very severe or even fatal secondary complications. This is primarily the case if the detached thrombus is washed away and in the form of an embolus comes to rest in smaller vessels, most effectively obstructing these and as a consequence causing the sufficient perfusion of the affected areas to be endangered. Resulting disease states may involve, for example, strokes, heart attacks or thromboses.
  • dual platelet inhibition is nowadays common practice as a rule to reduce the risk of thrombosis in the event surgery or interventions are necessary.
  • the patient is usually given a first dose of a combination of platelet aggregation inhibitors, in particular a combination of acetylsalicylic acid (ASA) and clopidogrel, before the intervention or surgery and must continue to take these regularly for a certain period of time after the procedure.
  • ASA acetylsalicylic acid
  • clopidogrel a combination of platelet aggregation inhibitors
  • these are usually applied instead of the clopidogrel in combination with ASS. Examples are prasugrel or ticagrelor.
  • the disadvantage of the dual platelet inhibition procedure is that it is systemic and therefore also has a systemic effect.
  • the patient thus faces a higher bleeding risk as a whole.
  • FIGS. 1 and 2 are photographs of plate specimens showing the difference in platelet adhesion between an uncoated plate and a coated plate.
  • a medical device as proposed by the invention essentially comprises at least a substrate and a functional layer.
  • the functional layer exhibits biomimetic and/or biorepulsive properties.
  • the substrate itself is usually still covered by a carrier layer, which comprises adhesion promoters, by means of which the functional layer can be bonded to the substrate.
  • adhesion promoters are silane adhesion promoters.
  • other adhesion promoters for example polyolefinic adhesion promoters or adhesion promoters based on titanates or zirconates may also be employed.
  • adhesion promoters include
  • the adhesion promoters should comprise functional groups via which the adhesion promoter is capable of reacting with the functional layer, so that as a rule covalent bonding is possible.
  • the substrate shall allow bonding to take place with an adhesion promoter.
  • substrates shall be referred to as ‘coatable substrates’.
  • coatable substrates comprise substrates the surface of which is sufficiently reactive and/or sufficiently activatable to at least partially form bonds with an adhesion promoter or also directly with the functional layer.
  • the bonds between the substrate and adhesion promoter preferably comprise covalent bonds.
  • coatable substrates may therefore be of very different nature and, in particular, comprise oxidizable substrates and combinations thereof.
  • these are metals such as nickel, titanium, platinum, iridium, gold, cobalt, chromium, aluminum, iron or alloys as well as combinations thereof.
  • a metal may also be coated with another metal for instance, with the carrier layer and the functional layer being applied to the outer metal layer.
  • Substrates in which the basic metal is covered by an oxide layer shall also count among coatable metals.
  • Other coatable substrates are glasses.
  • Coatable substrates within the meaning of the present invention may also be various plastics, such as polyamides (PA), polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polylactides (PLA), polyester, polyether, polyurethane, polyolefins, as well as relevant block copolymers.
  • PA polyamides
  • PTFE polytetrafluoroethylene
  • ePTFE expanded polytetrafluoroethylene
  • PLA polylactides
  • polyester polyether
  • polyurethane polyolefins
  • an adhesion promoter is needed for metallic or oxidic surfaces, it is not always employed when polymers are used as substrate.
  • an appropriate adhesion promotion may be achieved by silanization, that is the chemical bonding of silicon compounds, in particular silane compounds, to at least parts of their surface.
  • silanization that is the chemical bonding of silicon compounds, in particular silane compounds, to at least parts of their surface.
  • silicon and silane compounds attach, for example, to hydroxy and carboxy groups.
  • polyolefins which include chlorinated polyolefins (CPO) or acrylated polyolefins (APO).
  • the present invention is not limited to coatings of the plastics and metals named hereinbefore, which in fact are to be understood only as examples. In principle, the invention is aimed at coatings of all conceivable materials that constitute a coatable substrate within the meaning of this invention.
  • the silane may have the general formula RSiX 3 .
  • relevant compounds having several silicon atoms also count among the silane compounds.
  • silane derivatives in the form of organosilicon compounds are regarded as silane compounds in accordance with the invention. Accordingly, silane compounds in the sense of the invention are not only to be understood as substances comprising a silicon skeleton and hydrogen and being designated as silanes.
  • the matrix of the functional layer is covalently bonded to the carrier layer or substrate and is preferably synthesized by graft polymerization, with the functional layer being produced on the carrier layer or substrate.
  • the functional layer substantially comprises a complex, highly branched, hydrophilic matrix consisting of a plurality of molecules each having a main chain as polymer backbone with each having a plurality of side chains.
  • the main and/or side chains may form bonds with other main and/or side chains.
  • Other matrix-forming mono-, oligo- and polymers can be integrated into these main and side chains without being themselves covalently bonded to the carrier layer.
  • the main chain may comprise at least partially polymerized vinyl, allyl, acrylic or methacrylic compounds or derivatives thereof and/or isomers thereof or combinations thereof.
  • the side chains particularly comprise mono- and/or oligosaccharides, with reduction products of mono- or oligosaccharides being also understood as such, in particular sugar alcohols (alditols).
  • reduction products of mono- or oligosaccharides being also understood as such, in particular sugar alcohols (alditols).
  • oxidized mono- and/or oligosaccharides may also occur, with the oxidized form also being understood as mono- or oligosaccharide.
  • the medical device proposed by the invention comprises at least a substrate with a coating, said coating preferably comprising a carrier layer present on the substrate and a functional layer present on the carrier layer.
  • the carrier layer essentially comprises the adhesion promoters, which in most cases are covalently bonded to the substrate.
  • non-covalently bonding adhesion promoters are also known, for example those that attach to the substrate via a complex bond.
  • Preferred adhesion promoters are silicon compounds and polyolefinic adhesion promoters.
  • the functional layer comprises at least one functionalized sugar alcohol, via which the functional layer is covalently bonded to the carrier layer.
  • a preferred sugar alcohol of the functional layer corresponds in its non-functionalized form to a sugar alcohol of the molecular formula C 6 H 14 O 6 , for example sorbitol, and/or its derivatives, for example sorbitan, and/or its isomers, such as for instance mannitol.
  • “In its non-functionalized form” means that the molecular formula referred to represents the molecular formula of the non-functionalized sugar alcohol, but should also include, where appropriate, its derivatives and/or isomers.
  • the term functionalization shall be understood to indicate the introduction of a function into the compound permitting an attachment to the substrate, the carrier layer and/or to compounds already attached previously to the carrier layer or substrate.
  • the functional layer that forms part of the invention also comprises functionalized variants of the sugar alcohol of the molecular formula C 6 H 14 O 6 and/or its derivatives and/or its isomers. It is particularly clear to those skilled in the art that the functional layer comprises a complex matrix that can be created by polymerization of the applied, functionalized sugar alcohols.
  • derivatives shall be understood to comprise, in particular, all cyclic and/or heterocyclic compounds derivable from the substance, and shall even more precisely comprise all cyclic and heterocyclic compounds that can be derived from the substance by dehydration. Furthermore, the oxidized form of a compound is also regarded as a derivative.
  • the relevant sugar alcohol or the sugar alcohols are functionalized via at least one reactive group, wherein the reactive group preferably comprises a reactive multiple, in particular double bond and wherein said reactive double bond is preferably an acrylic group.
  • the reactive group preferably comprises a reactive multiple, in particular double bond and wherein said reactive double bond is preferably an acrylic group.
  • Other functional groups that can be suitably used for polymerization and do not necessarily have to have a reactive double bond are known to those skilled in the art and, for instance, comprise methacrylic groups, vinyl groups or allyl groups.
  • the sugar alcohols of the functional layer are at least partially polymerized among each other.
  • the medical device comprises at least one substrate provided with a coating, with said coating comprising a functional layer.
  • the functional layer comprises at least one functionalized monosaccharide, with the monosaccharides being covalently attachable to the carrier layer and oligomerizing or polymerizing taking place only upon bonding to the carrier layer.
  • the coating comprises a carrier layer located on the substrate, with the functional layer in turn being bonded to the carrier layer.
  • the bonds formed may be covalent bonds, however, may also be other bonds such as complex bonds.
  • the carrier layer comprises essentially the adhesion promoters that are bonded to the substrate.
  • Preferred adhesion promoters are silicon compounds and polyolefinic adhesion promoters.
  • the monosaccharide of the functional layer preferably comprises at least one sugar alcohol and/or its derivatives and/or its isomers.
  • a preferred sugar alcohol of the functional layer corresponds in its non-functionalized form to a sugar alcohol of the molecular formula C 6 H 14 O 6 , such as sorbitol, and/or its derivatives, for example sorbitan, and/or its isomers, for instance mannitol.
  • sorbitol and/or its derivatives, for example sorbitan, and/or its isomers, for instance mannitol.
  • the structure of sorbitol is shown below:
  • the functional layer that forms part of the invention comprises functionalized variants of the sugar alcohol of molecular formula C 6 H 14 O 6 and/or its derivatives and/or its isomers.
  • the functional layer comprises a complex matrix that has been created by polymerization of the applied, functionalized monosaccharides.
  • the monosaccharides of the functional layer can at least be partially polymerized among each other.
  • the monosaccharide is preferably functionalized via at least one reactive group, wherein the reactive group preferably comprises a reactive multiple bond, in particular a double bond, and wherein said reactive double bond preferably is an acrylic group.
  • the reactive group preferably comprises a reactive multiple bond, in particular a double bond
  • said reactive double bond preferably is an acrylic group.
  • Other function groups that can be suitably employed for polymerization and do not necessarily have to have a reactive double bond are known to those skilled in the art and, for instance, comprise methacrylic groups, vinyl groups or allyl groups.
  • the solution from which the functional layer of the coating proposed by the invention is made up may comprise one or a multitude of the following substances:
  • the structure of the functional layer can be varied via the specific composition of the substances. It is thus possible, for example, to create more closely meshed functional layers by increasing the proportion of crosslinkers or to create less crosslinked functional layers with longer linear ranges by causing the proportion of crosslinkers to be decreased.
  • the advantage of the inventive coating is seen in the fact that the functional layer possesses biomimetic or biorepulsive properties and is not recognized by thrombocytes as foreign to the body, but rather as originating within the body. Accordingly, the functional layer proposed by the invention does not trigger any reaction of the thrombocytes, in particular does not give rise to adhesion or aggregation reactions.
  • glycocalyx coats the cells of blood vessels with a kind of mucus layer and consists of various polysaccharides that are covalently linked to the membrane proteins (glycoproteins) and membrane lipids (glycolipids).
  • the biorepulsive effect of the coating according to the invention is based on the principle of steric repulsion effects.
  • the space available to the oligomers and polymers on the surface is reduced when a protein intrudes on this space, i.e. an approaching protein forces the oligomers and polymers on the surface to adopt an energetically less favorable conformation. This results in an overall repulsive force acting on proteins. It is also possible that the displacement of water molecules from the coating results in a repulsive osmotic force acting against proteins.
  • this principle of action means that the adherence of thrombocytes is prevented because there are no or only a few proteins on the surface that are suitable for bonding so that the platelet adhesion is significantly reduced.
  • Another advantage of the inventive coating is that, via the intermediate step of adhesion promotion, the coating covers only those surfaces and structures of the medical device which are capable of being activated for the relevant adhesion promoters and in particular have in fact been activated. Upon application of the functional layer solution it is thus possible to place the complete medical device into the functional layer solution without having to additionally protect areas that are not to be coated.
  • Such a selective coating offers advantages described hereinbefore for a plurality of medical devices and at least for those devices which are made of different materials, in which case the relevant coating is to be applied only on some of these materials.
  • the coating proposed by the present invention allows the coating process to activate only those parts/areas of the medical device that are intended to subsequently carry the functional layer. It is also conceivable that the medical device is already designed in such a way that the parts to be coated consist of substances that are capable of being activated for adhesion promotion.
  • Medical devices provided with the inventive coating are particularly suitable for endovascular, neurovascular and cardiovascular fields of application; however, the coating thus proposed by the invention can always be expediently applied on all medical devices that come into contact with blood.
  • the inventive coating was subjected to a series of in vitro tests in order to ascertain the effectiveness of the coating proposed by the present invention.
  • one uncoated small nitinol plate specimen and one small nitinol plate specimen silanized and subsequently coated with polymerized sorbitol acrylate in accordance with the invention were incubated with heparinized whole blood for a period of 10 minutes per test series.
  • the adhesion of platelets was then determined by fluorescence microscopy with the aid of fluorescence-labelled CD61 antibodies.
  • the adhesion of platelets/thrombocytes to the nitinol plate specimens coated in accordance with the invention was found to be significantly lower than that of the uncoated nitinol plates.
  • FIG. 1 shows an uncoated small nitinol plate specimen after 10 minutes incubation time with heparinized whole blood at 10 ⁇ magnification under the fluorescence microscope. The adhesion of a multitude of CD61 positive platelets is clearly visible.
  • FIG. 2 shows a coated small nitinol plate specimen after 10 minutes incubation time with heparinized whole blood at 10 ⁇ magnification under the fluorescence microscope. Only a few attached CD61 positive platelets can be recognized.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Surgery (AREA)
  • Chemical & Material Sciences (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Materials Engineering (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Laminated Bodies (AREA)
  • Paints Or Removers (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US16/612,994 2017-05-17 2018-05-17 Coating for medical devices Active 2039-11-07 US11779686B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE102017110748 2017-05-17
DE102017110748.7 2017-05-17
DE102017111486.6A DE102017111486A1 (de) 2017-05-17 2017-05-24 Beschichtung für Medizinprodukte
DE102017111486.6 2017-05-24
PCT/EP2018/062848 WO2018210989A1 (de) 2017-05-17 2018-05-17 Beschichtung für medizinprodukte

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US20200215238A1 US20200215238A1 (en) 2020-07-09
US11779686B2 true US11779686B2 (en) 2023-10-10

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Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102021106472A1 (de) 2020-12-22 2022-06-23 Acandis Gmbh Intravaskuläres Implantat und Herstellungsverfahren
WO2022135878A1 (de) 2020-12-22 2022-06-30 Acandis Gmbh Intravaskuläres implantat und herstellungsverfahren
JP2024505199A (ja) * 2021-01-26 2024-02-05 フェノックス ゲーエムベーハー コーティングされた医療機器
DE102021102377A1 (de) 2021-02-02 2022-08-04 Phenox Gmbh Beschichtung für Medizinprodukte
DE102022114767A1 (de) 2022-06-13 2023-12-14 Phenox Gmbh Endovaskuläre Vorrichtung mit Führungsdraht
WO2024018367A1 (en) 2022-07-22 2024-01-25 Phenox Gmbh Apparatus and method for treating vasospasm

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070065483A1 (en) * 2005-09-21 2007-03-22 Chudzik Stephen J In vivo formed matrices including natural biodegradable polysaccharides and uses thereof
US20080004410A1 (en) 2006-06-30 2008-01-03 Yu-Chin Lai Hydrophilic macromonomers having alpha,beta-conjugated carboxylic terminal group and medical devices incorporating same
WO2008006911A1 (en) 2006-07-14 2008-01-17 Biocompatibles Uk Limited Coated implant
US20140249614A1 (en) * 2009-03-06 2014-09-04 The Regents Of The University Of California Thin film vascular stent and biocompatible surface treatment

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6368658B1 (en) 1999-04-19 2002-04-09 Scimed Life Systems, Inc. Coating medical devices using air suspension
US6200626B1 (en) * 1999-05-20 2001-03-13 Bausch & Lomb Incorporated Surface-treatment of silicone medical devices comprising an intermediate carbon coating and graft polymerization
CN1100082C (zh) * 2000-04-18 2003-01-29 四川大学 医用高分子材料表面润滑改性方法
GB0410749D0 (en) 2004-05-14 2004-06-16 Dow Corning Ireland Ltd Coating apparatus
US20070264509A1 (en) * 2006-05-11 2007-11-15 Yu-Chin Lai Copolymer and Medical Device with the Copolymer
WO2009043174A1 (en) 2007-10-05 2009-04-09 Interface Biologics Inc. Oligofluorinated cross-linked polymers and uses thereof
DE102010020940B4 (de) 2010-05-19 2014-09-25 Heraeus Medical Gmbh Antibiotische Beschichtung
DE102010022588A1 (de) 2010-05-27 2011-12-01 Hemoteq Ag Ballonkatheter mit einer partikelfrei Wirkstoff-abgebenden Beschichtung
DE102010051740A1 (de) * 2010-11-19 2012-05-24 Phenox Gmbh Thrombektomievorrichtung
KR101304217B1 (ko) 2011-09-09 2013-09-05 오스템임플란트 주식회사 친수성 보습막이 코팅된 치과용 임플란트 및 그 제조 방법
WO2013071173A1 (en) * 2011-11-11 2013-05-16 Dacuycuy Nathan John Devices for removing vessel occlusions

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070065483A1 (en) * 2005-09-21 2007-03-22 Chudzik Stephen J In vivo formed matrices including natural biodegradable polysaccharides and uses thereof
US20080004410A1 (en) 2006-06-30 2008-01-03 Yu-Chin Lai Hydrophilic macromonomers having alpha,beta-conjugated carboxylic terminal group and medical devices incorporating same
WO2008006911A1 (en) 2006-07-14 2008-01-17 Biocompatibles Uk Limited Coated implant
US20090317443A1 (en) * 2006-07-14 2009-12-24 Biocompatibles Uk Limited Chapman House Coated implant
US20140249614A1 (en) * 2009-03-06 2014-09-04 The Regents Of The University Of California Thin film vascular stent and biocompatible surface treatment

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
International Search Report from International Application No. PCT/EP2018/062848 dated Sep. 13, 2018.

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US20200215238A1 (en) 2020-07-09
WO2018210989A1 (de) 2018-11-22
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BR112019024090A2 (pt) 2020-06-02
DE102017111486A1 (de) 2018-11-22
KR20200010280A (ko) 2020-01-30
AR111873A1 (es) 2019-08-28
KR102380344B1 (ko) 2022-03-31
CN110636871A (zh) 2019-12-31
JP7249290B2 (ja) 2023-03-30
CA3060672C (en) 2023-02-14
EP3551242A1 (de) 2019-10-16
ES2864526T3 (es) 2021-10-14
CA3060672A1 (en) 2019-11-12
AU2018268312B2 (en) 2021-05-20
EP3551242B1 (de) 2021-01-13
JP2020520256A (ja) 2020-07-09
AU2018268312A1 (en) 2019-11-28
DE102017011956A1 (de) 2018-11-22

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